Combination Chemotherapy Compared With Hormone Therapy in Treating Patients With Recurrent, Stage III, or Stage IV Endometrial Cancer

Gynecologic Oncology Group (GOG)

Status and phase: Terminated; Phase 3

Conditions: Endometrial Cancer

Treatments: Drug: doxorubicin hydrochloride; Drug: megestrol acetate; Drug: paclitaxel; Biological: filgrastim; Drug: tamoxifen citrate; Drug: cisplatin

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00016341

CDR0000068624

GOG-0189

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Estrogen can stimulate the growth of tumor cells. Hormone therapy using tamoxifen and megestrol may fight endometrial cancer by blocking the absorption of estrogen. It is not yet known whether chemotherapy is more effective than hormone therapy in treating endometrial cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with that of hormone therapy in treating patients who have recurrent, stage III, or stage IV endometrial cancer.

Full description

OBJECTIVES:

• Compare the progression-free survival and response of patients with stage III or IV or recurrent endometrial cancer treated with doxorubicin, cisplatin, paclitaxel, and filgrastim (G-CSF) vs tamoxifen and megestrol.
• Compare the survival of patients treated with these regimens.
• Determine if progesterone receptor status provides information on whether patients are more likely to benefit from chemotherapy.
• Compare the toxicity profiles of these treatment regimens in these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, cross-over, multicenter study. Patients are stratified according to progesterone receptor status (negative vs positive). Patients are randomized to 1 of 2 treatment arms.

• Arm I:Patients receive chemotherapy comprising doxorubicin IV over 15-30 minutes followed by cisplatin IV over 1 hour on day 1; paclitaxel IV over 3 hours on day 2; and filgrastim (G-CSF) subcutaneously beginning on day 3 and continuing for 10 days. Chemotherapy repeats every 21 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.
• At time of disease progression, patients cross-over to hormonal therapy as in arm II.
• Arm II: Patients receive hormonal therapy comprising oral megestrol twice daily on weeks 1-3 followed by oral tamoxifen twice daily on weeks 4-6. Hormonal therapy repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.

At time of disease progression, if patients have not previously been enrolled on arm I, patients cross-over to receive chemotherapy as in arm I.

Quality of life is assessed at baseline, 6 weeks, time of progression, and then after 6 weeks on cross-over therapy.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 630 patients will be accrued for this study within 42 months.

Sex: Female

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed primary stage III or IV or recurrent endometrial cancer

• Poor curative potential with radiotherapy or surgery (alone or in combination)

• Measurable disease

  • At least one lesion accurately measured in at least one dimension

    • At least 20 mm by conventional techniques, including palpation, x-ray, CT scan, or MRI OR
    • At least 10 mm by spiral CT scan

  • Disease in a previously irradiated field as sole site of measurable disease allowed only if clear progression after completion of radiotherapy

• Estrogen receptor(ER)/progesterone receptor (PR) status of primary tumor required

  • ER/PR status of measurable tumor optional

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• GOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Platelet count at least 100,000/mm^3
• Granulocyte count at least 1,500/mm^3

Hepatic:

• Bilirubin normal
• SGPT no greater than 3 times upper limit of normal

Renal:

• Creatinine no greater than 1.6 mg/dL

Cardiovascular:

• LVEF at least 50%
• No third-degree or complete heart block, unless pacemaker is in place
• Other conduction abnormalities or cardiac dysfunction allowed at the investigator's discretion
• No history of deep venous thrombosis
• No uncontrolled angina

Pulmonary:

• No history of pulmonary embolus

Other:

• No other malignancy within the past 5 years except nonmelanoma skin cancer
• No concurrent medical illness that would preclude study
• No serious uncontrolled infection
• No serious peripheral neuropathy
• No circumstances that would preclude study compliance
• No sensitivity to E. coli-derived drug preparations

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior biologic therapy allowed

Chemotherapy:

• No prior cytotoxic chemotherapy, including chemotherapy for radiosensitization

Endocrine therapy:

• No prior hormonal therapy for endometrial cancer

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy involving the whole pelvis or more than 50% of the spine

Surgery:

• See Disease Characteristics

Other:

• Concurrent cardiac conduction-altering medications such as digitalis, beta blockers, or calcium channel blockers allowed at the investigator's discretion